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Mirtazapine added to SSRIs or SNRIs for resistant depression: EBM and the Declaration of Helsinki.

The publication of the trial adding mirtazapine to SSRIs or SNRIs for resistant depression (MIR) deserves comment.(1)

First, could Kessler and colleagues provide data about psychological interventions, before prescribing SSRIs or SNRIs as well as after their failure? Indeed, most episodes of depression that persist are often successfully treated with specific psychosocial interventions, notably cognitive behavioural therapy (CBT) or behavioural activation as a first line. These treatments, robustly evidence-based in the real-life setting and over the long term,(2,3) are often preferred by patients(4) and known to improve self-esteem, agency, and social functioning.(5)

Second, were patients informed about NICE recommendations for “inadequate response to initial interventions”? Eg. (1.5.1.2) “For people with moderate or severe depression, provide a combination of antidepressant medication and a high-intensity psychological intervention.”(6) The use of a placebo when a recommended treatment is available is a breach of the Helsinki declaration, even more considering the duration of this trial (52 weeks).

Third, why were some patients prescribed SNRIs although NICE recommends “SSRI in a generic form …” (1.5.2.2). More specifically why were prescriptions of escitalopram and duloxetine allowed in the protocol? There is no evidence that escitalopram or citalopram are superior in terms of efficacy compared to other antidepressants. In contrast, robust documentation has existed since 2001 linking them to serious cardiovascular adverse effects (QT prolongation and deadly torsades de pointes).Similarly, duloxetine has no efficacy advantage versus other antidepressants but has the potential for life-threatening liver injury and severe skin reactions, including Stevens–Johnson syndrome.(7)